NETTER-P Lutathera adolescent

Advanced Accelerator Applications

This study will enroll 8 adolescent patients 12 – < 18 years old with somatostatin receptor-positive GEP NETs. If deemed necessary, more than 8 patients may be enrolled into the study, e.g. in case that a patient is not evaluable for the primary dosimetry analysis

Interventional, open-label, single-arm study

Phase II

8 patients en FRANCE

Dr Anne-Laure Giraudet

France

Centre Léon Berard, Lyon – Dr Anne-Laure Giraudet

Primary:

• Evaluate organ absorbed radiation doses from PRRT with Lutathera in adolescent patients with SSTR-positive GEP-NETs
• Evaluate safety and tolerability of Lutathera in adolescents with SSTR-positive GEP-NETs

Secondary:

• Evaluate cumulative safety of Lutathera in adolescents with SSTR-positive GEP-NETs
• Evaluate long-term safety of Lutathera in adolescents with SSTR-positive GEP-NETs
• Perform comparative assessment of dosimetry and pharmacokinetics (PK) in adolescent patients and adults using the model developed for the clinical study

1. Presence of metastasized or locally advanced, inoperable (curative intent), histologically proven, G1 or G2 (Ki-67 index ≤20%), well differentiated GEP-NET.
2. Patients from 12 to < 18 years of age at the time of enrollment.
3. Expression of somatostatin receptors confirmed by a somatostatin receptor imaging (SRI) modality within 3 months prior to enrollment, with tumor uptake observed in the target lesions more or equal to the normal liver uptake.
4. Performance status as determined by Karnofsky score ≥ 50 or Lansky Play-Performance Scale score ≥ 50.
5. Parent’s ability to understand and the willingness to sign a written informed consent document for adolescents from 12 to < 18 years of age. Adolescents will sign assent along with parental/legal guardian consent or will co-sign consent with parent/legal guardian in accordance with local regulation, prior to participation in the study.

1. Laboratory parameters:
   • Estimated creatinine clearance calculated by the Cockroft-Gault method < 70 mL/min
   • Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2×109/L; platelets <75×109/L.
   • Total bilirubin >3 x ULN for age.
   • Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
2. Established or suspected pregnancy.
3. Breastfeeding female patients unless they accept to discontinue breastfeeding from the 1st dose until 3 months after the last administration of study drug.
4. Female patients of child-bearing potential, unless they are using highly effective methods of contraception during treatment and for 6 months after the last dose of Lutathera (see details in the Appendix 1).
5. Sexually active male patients, unless they agree to remain abstinent or be willing to use effective methods of contraception.
6. Patients for whom in the opinion of the investigator other therapeutic options are considered more appropriate than the therapy offered in the study, based on patient and disease characteristics.
7. Current spontaneous urinary incontinence.
8. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
9. Hypersensitivity to the study drug active substance or to any of the excipients.
10. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
11. Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.
12. Patients who received any investigational agent within the last 30 days.
13. Prior therapies and procedures as detailed in Section 5.2.